Transcatheter arterial chemoembolization (TACE) is a well-tolerated and widely used, targeted treatment for advanced liver tumors [1]. However, this procedure is associated with a risk of ischemic cholecystitis. The diagnosis of ischemic cholecystitis can be difficult given that it can sometimes mimic gallbladder metastasis, particularly in patients with a history of primary cancer treated with TACE with drug-eluting beads (DEB). The prevalence of post-TACE ischemic cholecystitis is between 0.3% and 10%. It is more prevalent in right lobar chemoembolization, likely due to the origin of the cystic artery from the right hepatic artery [1],[2], or radiation injury from the accumulation of 90Y particles [3]. Patients commonly experience abdominal pain accompanied by systemic symptoms such as fatigue, fever, and a group of symptoms referred to as post-embolization syndrome [4].

In a retrospective study, metastasis to the gallbladder was reported in 4.8% of all gallbladder malignancies [5]. Despite being rare, metastatic melanoma of the gallbladder, which is the most common form of metastatic disease of the gallbladder, can produce symptoms that masquerade as cholecystitis [6]. A poor prognosis was observed in patients who underwent acute cholecystitis cholecystectomy. Wakasugi et al. (2012) described a case of hepatocellular carcinoma metastasis to the gallbladder. During their hepatic resection, they performed a cholecystectomy to prevent postoperative cholecystitis. Despite not finding metastasis on the gallbladder macroscopically, pathological analysis confirmed the presence of tumor cells. Wakasugi et al. highlighted how difficult a preoperative diagnosis of hepatocellular carcinoma to the gallbladder can be, especially given the incidence being as low as 2.8%, and the importance of histopathologic analysis for confirmation [7].

Ischemic cholecystitis exhibits similar macroscopic intraoperative findings as metastasis with imaging findings not being reliable to differentiate in many cases. The differential should be investigated using a combination of multimodality imaging, CT findings of well-defined enhancing polypoid lesions with arterial enhancement and portal washout [8], laboratory parameters, histopathological examination, and patterns of gallbladder wall thickening [9].

The patient was a 53-year-old male with a history of compensated cirrhosis secondary to chronic hepatitis C virus (HCV) infection, complicated by hepatocellular carcinoma (HCC) localized to the right hepatic lobe. The patient’s surgical plan included a partial hepatectomy of segment 5, along with a cholecystectomy, following transarterial chemoembolization (TACE) for the treatment of HCC.

Preoperative planning involved a diagnostic mapping angiography procedure. Catheterization was achieved of the right hepatic artery, including the inferior pole branch of segments 6 and 7, as well as the superior branch of segment 8. No anatomical variants were identified. Embolization was subsequently conducted using Embozene drug-eluting beads (100 microns), with a total of one vial used for the procedure. Yttrium-90 (Y90) Theraspheres, with a prescribed activity of 9.5 GBq for segment 7 and 4.0 GBq for segment 6, were then administered. The targeted delivery achieved a 99% dose distribution.

The patient had persistent disease identified on post-treatment imaging and was offered resection. Intraoperatively, the liver appeared to be cirrhotic with abdominal stigmata of portal hypertension. An abnormal appearance of the gallbladder infundibulum and neck was noted, a thick white appearance with a palpable mass. The gallbladder was resected and sent to the pathology unit for a frozen section to rule out metastatic disease. The palpable mass in the gallbladder which was noted to be consistent with a gall stone and the hard white area was consistent with chronic inflammation with embolic beads. Though there was suspicion of metastasis based on the gross appearance of the gallbladder, the final postoperative pathological diagnosis revealed cholelithiasis and chronic cholecystitis with chemoembolization beads with no carcinoma, as shown in Figure 1, Figure 2, Figure 3.

Transcatheter arterial chemoembolization is a commonly performed procedure used to treat patients with hepatocellular carcinoma (HCC) using drug-eluting beads (DEB) which reduce the vascular supply to the tumor. It is reported to have a 5% risk of major complications with a 1% risk of death. Major complications include hepatic failure, abscess formation, ischemic cholecystitis, pancreatitis, and pulmonary embolization [10].

Gallbladder ischemia after chemoembolization has been documented by various studies. According to the literature, the incidence ranges between 0.3% and 10% [11]. The risk of ischemic cholecystitis is elevated when the embolization beads escape into the proximal segment of the right hepatic artery or the proper hepatic artery or in a gallbladder where the cystic artery may originate from the left hepatic or superior mesenteric artery. Furthermore, the chemoembolization of lesions located in liver segments IV or V may also lead to an increased risk of cholecystitis [1], [12].

Ischemic cholecystitis’s clinical presentation can mimic that of other TACE complications, creating diagnostic challenges. Ultrasound and computed tomography (UT) imaging can be used to differentiate between cholecystitis and liver ischemia or pancreatitis. Additionally, in a case series of liver embolization, Chuang and Wallace [13] described that instances of right upper quadrant pain post-embolization could be particularly attributed to gallbladder ischemia, differentiating it from pain caused by liver ischemia or pancreatitis.

Differentiating ischemic cholecystitis and gallbladder metastasis is more difficult given the inconsistent imaging findings typically seen with cancer, but it carries significant clinical implications. Kim et al. found that while patients with gallbladder cancer typically showed focal enhanced wall thickening as opposed to diffuse in cholecystitis, irregular mural thickening and enhancement can be seen with cancer [8]. In patients diagnosed with gallbladder metastasis, widespread disease is commonly observed at the time of diagnosis and would warrant further oncological care such as chemotherapy and/or radiation therapy [14].

As seen in our case, it is important to confirm the intraoperative diagnosis by obtaining a frozen section of the gallbladder to analyze the histopathological findings and look for the waxy white gross appearance of ischemic cholecystitis with an absence of cancerous cells. This distinction is crucial to discern ischemic cholecystitis from direct extensions of malignancy or metastasis. Hence determining appropriateness of proceeding with liver resection.

Most studies documenting cholecystitis post-TACE, employed conservative management as the primary treatment approach. A study of ischemic complications after TACE by Tarazov et al. (2000) reported that ischemic cholecystitis could be successfully treated with percutaneous drainage and antibiotics [15]. It is crucial to emphasize the significance of cholecystectomy at the time of hepatectomy to minimize later complications and resolve patients’ symptoms effectively.

Differentiating gallbladder metastasis and ischemic cholecystitis can be difficult given the lack of reliable differences on imaging findings as well as macroscopic similarities. We describe a case of ischemic cholecystitis secondary to a TACE procedure that was intraoperatively suspected as gallbladder metastasis before pathological workup revealed the true diagnosis. This case highlights the importance of perioperative histopathological findings to confirm the diagnosis and to differentiate the complications of TACE. Accurate and timely diagnosis was essential to ensuring the patient received appropriate therapy.